Volume 10, Number 1
Researchers Recount Successes at NIDA 20th Anniversary Celebration
By Neil Swan, NIDA NOTES Contributing Writer
Some of NIDA's leading researchers paid tribute to the Institute at its recent 20th anniversary symposium celebrating progress in drug abuse research. The scientists listed a number of research advances that would not have been possible without the unparalleled scientific infrastructure NIDA developed to study all aspects of drug abuse and addiction.
"We've come a long way," building on basic research, since the Institute's birth, said NIDA Director Dr. Alan I. Leshner, who pledged a bigger, more triumphant 25th anniversary commemoration in 1999 that would mark significant new advances against drug abuse and addiction.
Several scientists participating in the day-long session held last September on the campus of the National Institutes of Health spoke about the important role research plays in advancing the effectiveness of treatment for drug abuse. They pointed to mounting data demonstrating that drug abuse treatment is practical, productive, and cost-effective.
"We've come a long way," building on
basic research, since the Institute's birth.
"Two big goals of drug abuse treatment are to reduce mortality and morbidity, and there is no doubt that treatment is successful in that regard," said Dr. Thomas J. Crowley of the University of Colorado. "Studies show that methadone maintenance works" by keeping patients alive and healthy, he told those at the symposium. In addition, treatment outcome data collected by Dr. Robert Booth and Dr. Crowley show that Denver "street addicts who chose to enter some form of treatment and then were followed for 6 months did dramatically better, in terms of reduced drug use," than did addicts who did not enter treatment, said Dr. Crowley.
Studies also show that methadone treatment is even more successful when accompanied by appropriate counseling and social services. A NIDA-funded study by Dr. A. Thomas McLellan and his colleagues at the Philadelphia Veterans Affairs Medical Center found that patients who receive counseling and psychiatric care in addition to methadone are more successful in reducing their levels of heroin use than those who receive only methadone. (See "Research Demonstrates Long-Term Benefits of Methadone Treatment," NIDA NOTES, November/December 1994, p. 1.)
Other speakers at the 20th anniversary celebration pointed to numerous basic research advances that have contributed to science's understanding of drug abuse. Dr. Solomon Snyder of Johns Hopkins University summarized the work that led to his historic discovery in 1972 of the opioid receptor, the molecular site in the brain where morphine, heroin, and other opiates initiate their actions on the body. More recently, Dr. Snyder has conducted research on nitric oxide. He has discovered that brain cells use the colorless gas to signal each other and that nitric oxide causes brain damage after a stroke. In his current research, he is trying to determine if nitric oxide can block long-term physiological change caused by drug abuse.
Dr. Snyder also is examining the role nitric oxide plays in the development of tolerance to morphine, a phenomenon that causes addicted people to seek increasing doses of morphine. These and other NIDA drug abuse studies, he said, "help us to learn a lot about basic science and vice versa."
The list of achievements in drug abuse and addiction research can be attributed in large part to "a relatively small, close-knit group of researchers who have been continuously supported by NIDA for 20 years," said Dr. Huda Akil, director of the Neuroscience Graduate Program at the University of Michigan. Recent accomplishments, such as the cloning 2 years ago of the genes for opioid receptors, bring drug abuse to the threshold of major new advances, although researchers know "we have a great deal still to learn," she said.
Dr. Louis S. Harris, a pioneer drug abuse researcher at the Medical College of Virginia of Virginia Commonwealth University, recounted the crusade of early addiction researchers to separate the pain-relieving properties of morphine from its addicting properties. These scientists developed a number of synthetic morphine-related analgesics, experimented with opiate molecules, and increased the potency of analgesics by as much as 50,000 times. In addition, they developed pure opioid antagonists useful in the treatment of narcotic overdoses and as medications for the treatment of opiate addiction; they also developed mixed opioid agonist-antagonist analgesics with a reduced dependence potential. However, they never reached their goal of completely separating analgesia from addiction--still a major quest, he said.
Dr. Gerald Friedland, an AIDS investigator at Yale University, cited a number of research accomplishments that have been made in defining the relationships between drug abuse and the spread of AIDS. These include documenting the extent of the problem; defining behavioral, social, and biological predictors of drug abuse-related transmission of HIV, the virus that causes AIDS; profiling the natural history and progression of HIV disease; studying the problems of women with AIDS; and characterizing an expanded spectrum for HIV disease related to drug use.
Injection drug use (IDU) is responsible for the second largest number of AIDS cases currently being reported in the United States, and the proportion of these cases is increasing, Dr. Friedland said. About 25 percent of U.S. AIDS cases are now attributed to injection drug use alone, he said.
Researchers have identified a number of IDU risk factors for HIV transmission, including the number of injections per month; the duration of IDU; the proportion of IDU conducted in "shooting galleries," hideaways where addicted persons gather to use drugs and share injection equipment; the extent to which needles are reused; the proportion of injections shared with a stranger; and the year of a person's last injection.
Researchers have demonstrated substantial IDU behavioral changes resulting in a reduction in the risk of spreading HIV, he noted. One key behavioral change--sharing fewer injections--can be related to providing sterile injection equipment to users, he added.
Strategies to curtail the spread of HIV are also a major part of NIDA's comprehensive research portfolio examining the special needs and concerns of women as they relate to drug abuse, said Dr. Loretta P. Finnegan, NIDA's former senior advisor on women's issues. A major NIDA-supported study of women, cocaine, and childbirth--that also examined the complicating factors of smoking, drinking, youthful pregnancy and motherhood, and sexually transmitted diseases, including AIDS--is now well into its second generation, she said. Another study being conducted by NIDA in collaboration with the National Institute of Child Health and Human Development and other Federal agencies is the largest, most comprehensive study of infants born to women who used cocaine or opiates during pregnancy. (See "What Does the Future Hold for Drug-Exposed Babies," NIDA NOTES, July/August 1993, p. 1.)
In all, NIDA has supported 20 perinatal research programs, Dr. Finnegan added. An Institute study drew national attention in September when it chronicled the troubling fact that 5.5 percent of pregnant American women report using some kind of abused substance during pregnancy, creating untold risks to their unborn children, Dr. Finnegan noted. (See "NIDA Survey Provides First National Data on Drug Use During Pregnancy")
Also discussed at the 20th anniversary symposium was the Institute's efforts to gather drug-use statistics. "NIDA has done a great deal in the 1,000-plus weeks of its existence," said Dr. Richard Clayton of the University of Kentucky. Epidemiological studies tell us who uses what drugs, to what extent, and with what consequences and also help determine where and why drugs are abused, he said.
But studies of drug-use trends must be carefully interpreted, he cautioned. Trend data that showed drug use rates on a general decline until 1993 led Congress and the public to assume false complacency because some observers of the data concluded that the cocaine use problem may be decreasing, he said. In reality, when cocaine users are divided into groups of heavy and light users, it is clear that drug use among the heavy cocaine users is actually increasing, said Dr. Clayton. This demonstrates the necessity of great care in evaluating and interpreting drug-use trend data, he said.
Another NIDA-supported researcher, Dr. Conan Kornetsky of Boston University, said that 20 years of research by a number of NIDA-supported investigators have overturned widely held stereotypes and simplistic cliches about drug abuse. Well into the 1970s, it was generally believed that drugs were abused primarily by two types of people: those with some underlying pathology and those who became addicted and then continued to take drugs to relieve the symptoms of withdrawal, he said. Although these are important contributing factors, the primary reason for drug abuse is the action that these drugs have on the brain reward systems--those areas of the brain involved in many natural rewards, he said.
Research during the past 20 years has delineated those structures and transmitters involved in reward systems, which are stimulated by abused substances, Dr. Kornetsky said. While dopamine has been implicated as the critical neurotransmitter mediating reward system pathways, recent studies indicate that other mediating neurotransmitters and structures also are involved. At the same time, cognitive and environmental conditions as well as genetics may also affect these other mediating transmitters and structures. Taken together, these external and internal factors may alter or even negate the rewarding effects of a drug, he noted.
Dr. Ralph Tarter of the University of Pittsburgh discussed vulnerability to drug abuse, noting that 7 percent to 10 percent of individuals exposed to illicit drugs become dependent on these drugs; about 15 percent of those who drink become dependent on alcohol. Three variables are involved in vulnerability to drug abuse: the common environment everyone shares, each individual's unique environment, and genetic factors, he said. Many studies, some involving twins, show that the unique environment is more important than the common environment in determining vulnerability, he said. Parentage, particularly that of the father, is also an important risk factor for drug abuse, Dr. Tarter noted.
Behavioral studies show that temperament traits, such as emotionality, activity, sociability, and impulsivity, are important childhood predictors of subsequent drug abuse, he said. "Preliminary findings indicate that we can predict with about 75 percent accuracy at age 10 which kids will use drugs by age 12," Dr. Tarter said. (See "Early Childhood Behavior and Temperament Predict Later Substance Use")
It is difficult to translate these and other findings about vulnerability into drug policy and decision-making, he said. For one thing, he explained, science needs a new terminology that avoids reliance on emotion-charged terms such as "impulsivity" and other current terminology for predictive temperament traits, he said.
Dr. Joseph V. Brady of Johns Hopkins University said that behavioral biology has made major advances that are being applied to the field of drug abuse research. It is now recognized that drug-seeking and drug-taking are learned--not innate--behaviors, he pointed out. This is an important conceptual change in the way addiction is viewed that has come about in the 20 years since NIDA began its work, he said.
The Institute has done a great deal not only to educate the public about addiction but also to recruit young scientists to enter the research field, he said. NIDA deserves praise for its unflagging support of drug abuse research and its career-guidance efforts to cultivate young scientists to become the "superstars of tomorrow" in addiction research, said Dr. Brady. He lauded NIDA for its "critical contributions over 20 years in the development and maintenance of a research infrastructure" for drug abuse studies that is unrivaled in the world.
From NIDA NOTES, January/February, 1995
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